Objectives: Depression and anxiety are two major categories of mental disorders that are highly prevalent in the general population. This study aims to explore the genetic modification effects of physical frailty on the morbidity of mental disorders.Methods: Using data from UK Biobank, we calculate genetic risk scores for depression, anxiety and mental disorders based on 37/44 single-nucleotide polymorphisms (SNPs) of Major Depressive Disorder (MDD) and 9/10 SNPs of anxiety. Frailty status was defined by a modified version of the frailty phenotype based on five individual components. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of depression and anxiety risk among groups with different frailty status.Results: Of 267,755 participants in UK Biobank, 4,905 (2%) were considered frail, 98,907 (37%) pre-frail and 163,943 (61%) not frail. Compared with the non-frail group, the pre-frail group (HR = 1.53; [95% CI:1.47-1.61]), and frail group (HR = 2.75; [95% CI:2.46-3.07]) were significantly associated with increased risk of depression. Per 1-number increment in frailty component counts were significantly associated with increased risk of mental disorders. In each genetic risk score (GRS) strata, people with pre-frailty and frailty suffered higher risks of mental disorders than the non-frail group.Conclusion: Our results indicate that physical frailty plays an important role in the incidence of mental disorders, even after adjustments for covariates, and patients with genetic individual differences are also affected. Therefore, it is crucial that while diagnosing mental disorders, professionals pay closer attention to those patients who present symptoms of frailty.
Keywords: Depression; anxiety; frailty; genetic risk; mental disorders.